Researchers from the University of Ottawa and the National Research Council of Canada, in collaboration with the Centre for Infection, Immunity, and Inflammation in Ottawa, have conducted a study exploring the potential impact of the SARS-CoV-2 virus on neurological health. The study aimed to investigate the link between the virus and various neurological complications, with a focus on mitochondrial dysfunction and the monoamine oxidase B (MAO-B) enzyme.
Neurological symptoms have been observed in a significant number of COVID-19 patients, with up to 70-80% of hospitalized patients experiencing them. While most of these symptoms resolve after the initial infection, some patients report persistent neurocognitive issues, often referred to as “long-COVID.” Autopsies of deceased COVID-19 patients have revealed viral antigens and RNA in brain tissue, suggesting that the virus can infect neurons, microglia, and astrocytes.
The SARS-CoV-2 spike (S) protein, responsible for the virus’s entry into host cells, binds to the angiotensin-converting enzyme 2 (ACE2) receptor, expressed in cells that line the blood-brain barrier (BBB) and the choroid plexus epithelium. This expression makes these cells potential entry points for the virus into the central nervous system (CNS). Additionally, the S protein can cross the BBB and affect brain metabolism and function.
Mounting evidence suggests that SARS-CoV-2 targets mitochondria, leading to disruptions in cellular energy metabolism similar to those seen in neurodegenerative diseases. The virus is associated with changes in mitochondrial morphology, alterations in bioenergetic function, increased production of reactive oxygen species (ROS), and decreased mitochondrial membrane potential. The S protein can interact with cellular proteins and modulate various cellular processes, including mitochondrial function.
Monoamine oxidase B (MAO-B), an enzyme located on the outer mitochondrial membrane, has structural similarities to the ACE2 receptor. Increased MAO-B activity is associated with neurodegenerative diseases, including Parkinson’s disease, where it contributes to mitochondrial dysfunction, increased ROS production, and dopaminergic neuron loss. The interaction between the S protein and MAO-B may alter neurotransmitter metabolism and contribute to neurodegenerative changes in COVID-19 patients.
The study conducted by the researchers showed that the S protein interacts with MAO-B and enhances its activity. It also disrupts mitophagy, the process of degrading dysfunctional mitochondria, leading to their accumulation. Neuron-like cells expressing the S protein were found to be more susceptible to neurotoxic insults. These findings support the role of MAO-B and mitochondrial dysfunction in the development of neurological complications associated with COVID-19.
Understanding the neurological implications of SARS-CoV-2 infection is crucial for providing effective treatment and improving the quality of life for COVID-19 survivors. Further research is needed to explore the therapeutic potential of MAO-B inhibitors in preventing or mitigating neurodegeneration induced by the virus. This study contributes valuable insights to the field of COVID-19 research by shedding light on the complex relationship between viral infection and neurological complications.